The goal of dengue prevention and control programs is cost-effective utilization of limited resources to reduce vector populations to levels at which they are no longer of significant public health importance. There is no clinical cure for dengue and a licensed vaccine is not currently available. An implicit assumption of the vector control approach is that as entomological risk increases so does the potential for dengue virus transmission and the incidence of severe forms of disease. The vector control approach emphasizes vector surveillance, with the objectives of maintaining Ae. aegypti populations below or close to transmission threshold values, slowing dengue virus transmission, and reducing sequential infections with heterologous serotypes that can increase the incidence of serious disease. However, no well-controlled field studies have been carried out to define the relationships between vector density and human infection. Using a prospective epidemiologic approach, we will define-in collaboration with personnel in Project 1 and the Core -the temporal and spatial relationships among entomological risk factors, incidence of human infection, and clinical disease manifestations. We will test the hypothesis that entomological risk (vector density) is positively correlated with the intensity of dengue virus transmission, incidence of clinical illness, and severity of dengue disease. All entomological, serological, and clinical data will be managed in a Geographic Information System so that we can analyze spatial and temporal patterns of dengue cases and entomological risk factors. In our first aim we will determine whether measures of risk associated with Ae. aegypti are positively correlated with the force of dengue virus transmission and the spectrum of clinical disease manifestations. We will use a novel study design in which we identify active dengue cases, follow contacts of those cases within a geographic radius of 100 m for a 2-week period, and characterize entomological parameters at the time of transmission in and around index and contact homes. In our second aim, we will test the relative importance of transmission in homes versus schools (1) indirectly by comparing entomological risk factors to the force of transmission and severity of disease and (2) directly using vector intervention. Our research is a test of the fundamental premise of current dengue control recommendations. We will be the first to intimately link, in time and space, dynamics in dengue transmission to entomological risk, incidence of human infection, and the severity of disease. The quantitative relationships between entomological risks and virus transmission that we will define are applicable to other arboviruses, including West Nile virus in North America.